This Clinical Research Center, now in Year 21, has been concerned with human neuromuscular diseases. The board objective is to elucidate the etiology and pathogenesis of these disorders, in order to either devise rational treatments for presently untreatable conditions or provide information that could guide sound genetic counseling. The emphasis has shifted in different periods of the grant, but we have concentrated on human patients. The current program includes two main themes: mitochondrial encephalomyopathies and autoimmune motor neuropathies. Center investigators have been active in both fields and have been collaborating for many years. These are three projects. Project 1 Bonilla and Schon will study mtDNA deletions in muscle and brain, using combined morphological and genetic approaches, including novel PCR-based methodologies. Project 2 King and Miranda will study genotype-phenotype relationships of mtDNA mutations in a novel, post-mitotic tissue culture system. Project 3 Latov, Lee, and Hays will study mechanisms by which exposure to Campylobacter jejuni may activate specific 'memory' B cells which recognize the bacterial complex oligosaccharides, resulting in production of pathogenic autoantibodies, using transgenic mouse technology as a key component. A clinical core DiMauro and Rowland will provide direction, administration, external consultation, clinical coordination, and share technical service to the project as a whole. As always, we have encouraged collaboration between the basic and clinical scientists.